水飞蓟宾纳米胶束的制备及其鼠体内药物动力学研究

 目的 以聚维酮-磷酯-胆酸盐三元胶束为载体制备水飞蓟宾纳米胶束,并考察其体外性质及鼠体内药动学行为。方法 制备水飞蓟宾纳米胶束;透射电镜观察胶束形态;光子相关光谱粒径仪测定粒径分布和Zeta电位;紫外分光光度法考察载 药胶束的含药量;高效液相色谱法测定小鼠血药浓度,BAPP2．0药动程序处理数据。结果 水飞蓟宾纳米胶束多呈球形,粒径 小于100 nm,平均粒径为61．2 nm,Zeta电位为-44．8 mV,含药量达到4．19 g·L^-1;浓度数据经二室模型拟合后表明,与参比制 剂相比水飞蓟宾纳米胶束在小鼠体内的K_a增大,达峰时间缩短,MRT延长,峰浓度和AUC_0～∞增加。结论 聚维酮-磷酯-胆酸 盐三元胶束有望成为难溶性药物的新型载体。

Preparation of silybin loaded nano-micelles and pharmacokinetic evaluation in mice

OBJECTIVE To prepare the PVP-lecithin-bile salt mixed nano-micelles containing silybin, and to evaluate the characters in vitro and pharmacokinetics in mice.METHODS The prepared nano-micelles were observed by transmission electron microscope. The Zeta potential and the diameters distribution of SLB nano-micelle were measured by photo correlation spectroscopy(PCS). The drug loading was determined by ultraviolet speetrophotometry. The SLB concentrations in mice blood samples were assayed by high-performance liquid chromatography (HPLC), and the data were analyzed with BAPP2.0 program package. RESULTS SLB nano-micelles were almost spherical, smaller than 100 nm with a mean diameter of 61.2 nm, and had a zetar potential of-44.8mV. The drug loading was 4.19 g·L^-1. The concentration-time data fitted of with a two-compartment model showed that, in comparison with the control preparation, the SLB nano-micelles accederated K_a, shortened t_max,prolonged the mean residenced time(MRT), and increased the ρ_max and AUC_0～∞.CONCLUSION The PVP-lecithin-bile salt mixed nano-micelles can be used as a new carrier for poorly water-soluble drugs.